No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission.

AIMS: Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined. METHODS AND RESULTS: In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR. CONCLUSION: This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients. CLINICAL TRIAL NUMBER: NCT01483755.

Is There Still a Role for Fibrinolysis in ST-Elevation Myocardial Infarction?

OPINION STATEMENT: Fibrinolysis had long been the reference treatment in patients with ST-Elevation Myocardial Infarction (STEMI). It was associated with a large reduction in mortality as compared with delayed or no reperfusion in patients managed early, within the first 2 hours from the onset of symptoms. Fibrinolysis also had well-known potential complications: cerebral haemorrhage, especially in patients beyond 75 years, and reinfarction. Primary percutaneous intervention (PCI) has overcome most of these limitations, but at a price: PCI-related delays that can reduce the expected benefit of primary PCI compared with fibrinolysis. That primary PCI is today the treatment of choice in patients with STEMI is no longer discussed. However, fibrinolysis should still maintain a role in the management of acute myocardial infarction (AMI) for three reasons. First, fibrinolysis is no longer a stand-alone treatment. Modern fibrinolytic strategies combine immediate fibrinolysis, loading dose of thienopyridines, and transfer to a PCI hospital for rescue or early PCI within 24 hours. These strategies capitalize on the hub-and-spoke networks that have, or should have, been built everywhere to implement primary PCI. The overall clinical results of these modern fibrinolytic strategies are now similar to those of primary PCI. Second, a substantial number of patients cannot be managed with primary PCI within the reasonable time thresholds set by the guidelines. In the case of long PCI-related delays, patients will benefit from fibrinolysis before or during transfer to a PCI hospital. Third, modern fibrinolytic strategies-immediate fibrinolysis followed by rescue or early PCI-may even offer the best results of all in a subset of patients. Patients of less than 75 years, managed within the first 2 hours and who cannot have immediate PCI, will fare better with a modern fibrinolytic strategy than with primary PCI. Guidelines advocate regional networks between hospitals with and without PCI capabilities, an efficient ambulance service and standardization of AMI management through shared protocols. These regional logistics of care are essential to take full advantage of fibrinolysis strategies. In order to check that these strategies are correctly applied, networks need ongoing registries, as well as benchmarking and quality improvement initiatives.